Abstract

Using atomistic molecular dynamics simulations,interaction of multiple synthetic random copolymers based on methacrylates on prototypical bacterial membranes is investigated. The simulations show that the cationic polymers form a micellar aggregate in water phase and the aggregate, when interacting with the bacterial membrane, induces clustering of oppositely charged anionic lipid molecules to form clusters and enhances ordering of lipid chains. The model bacterial membrane, consequently, develops lateral inhomogeneity in membrane thickness profile compared to polymer-free system. The individual polymers in the aggregate are released into the bacterial membrane in a phased manner and the simulations suggest that the most probable location of the partitioned polymers is near the 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) clusters. The partitioned polymers preferentially adopt facially amphiphilic conformations at lipid-water interface, despite lacking intrinsic secondary structures such as α-helix or β-sheet found in naturally occurring antimicrobial peptides.

Received 17 June 2014Accepted 06 August 2014Published online 26 August 2014

Acknowledgments:

K. Kuroda is a co inventor on a patent application filed by the University of Pennsylvania covering “Antimicrobial Copolymers and Uses Thereof.” The patent application has been licensed to Cellceutix (Beverly, MA). Cellceutix did not play a role in the design and conduct of this study, in the collection, analysis, or interpretation of the data, or in the preparation, review, or approval of the article.

All the simulations in this work have been carried out on 1024-cpu Annapurna cluster at The Institute of Mathematical Sciences, Chennai, India. This work was supported by NSF CAREER Award (KK, DMR-0845592). U.B. would like to acknowledge helpful discussions with Anish Mallick.